Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: EN-374.
- Who it may be relevant to
- Registry conditions: X-Linked Chronic Granulomatous Disease. Basic parameters: from 3 months · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, United Kingdom
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase 1/2 Open-Label, Single-Ascending-Dose Study of EN-374, a Helper-Dependent Adenoviral-Based Gene Therapy, in Participants With X-Linked Chronic Granulomatous Disease
Overview
The goal of this clinical trial is to evaluate the safety and potential efficacy of the EN-374 treatment regimen and identify a dose level for further evaluation in participants with x-linked chronic granulomatous disease. The main questions it aims to answer are: * safety of the EN-374 treatment regimen * effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
Detailed description
Chronic granulomatous disease (CGD) is a rare primary immune deficiency disorder characterized by recurrent bacterial or fungal infections starting in infancy. The x-linked form of CGD (X-CGD) is caused by mutations in the CYBB gene.
EN-374 is a helper-dependent adenoviral (HDAd)-based gene therapy in development for the treatment of X-CGD using an in vivo approach, which is administered by IV infusion, to genetically modify hematopoietic stem cells (HSCs) to express a wild-type CYBB gene. The EN-374 treatment regimen includes HSC mobilization, immune prophylaxis, EN-374 administration, and enrichment of genetically modified HSCs.
Adult participants with X-CGD will be enrolled into the dose-escalation part of the study. Following completion of the adult cohorts, then pediatric participants will be enrolled into the dose-expansion part of the study in decreasing age cohorts from ≥ 12 and \< 18 years of age, to ≥ 2 and \< 12 years of age, and finally to ≥ 3 months and \< 2 years of age.
Interventions
- Genetic EN-374
Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment
Primary outcome measures
- Safety of EN-374 [Time frame: From start of mobilization until Month 12]
Secondary outcome measures (1)
- Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity [Time frame: From infusion of EN-374 until Month 12]
Eligibility criteria
Inclusion criteria
- Male
- ≥ 18 years of age during dose escalation, then ≥ 3 months of age during dose expansion
- Diagnosis of X-CGD with DHR+ cells ≤ 5% and a pathogenic mutation in the CYBB gene
- History of at least 1 severe infection requiring medical intervention or chronic inflammatory disorder
- Does not have a suitable, available, and willing human leukocyte antigens (HLA)-matched (10/10) related donor
- Non-sterile male participants who are or may become sexually active with female partners of childbearing potential are required to use highly effective contraception
- Informed consent, with informed assent from capable participants
- Adequate organ function
Exclusion criteria
- Active bacteremia or fungemia
- History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- History or clinical evidence of any medical or social issues likely to put the participant at additional risk or to interfere with study conduct
- History of HSCT or granulocyte transfusions
- Known hypersensitivity to elements in the treatment regimen
- Undergone investigational gene therapy
- Treated with another investigational drug product within 30 days before screening
- Unable to comply with the visits and requirements of the protocol as determined by the Investigator
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 8 centers
- University of California, Los Angeles — Los Angeles
- University of California, San Francisco — San Francisco
- Johns Hopkins All Children's Hospital — St. Petersburg
- Boston Children's Hospital — Boston
- University of Minnesota — Minneapolis
- Columbia University Irving Medical Center, Morgan Stanley Children's Hospital — New York
- Duke University — Durham
- University of Utah, Primary Children's Hospital — Salt Lake City
United Kingdom · 1 center
- University College London Hospital — London
Identifiers
NCT: NCT06876363 · EN-374-101